Biochemical Aspects of Biochemical Aspects of Digestion of LipidsDigestion of Lipids
Dr. Amr S. Moustafa
OBJECTIVESOBJECTIVESBy the end of this lecture, the student
should be able to: ◦ Understand the process of digestion of
dietary lipids including, the organs involved, the enzymes required, and the end products.
◦ Implement the basic science knowledge of the process of lipid digestion to understand the clinical manifestations of diseases that involve defective lipid digestion and/or absorption (maldigestion and malabsorption syndrome)
Dietary LipidsDietary LipidsDietary lipids intake is ~81 g/day
Triacylglycerol is ~ 90%The remainder includes (10%):
CholesterolCholesterol esterPhospholipidsGlycolipidsFree fatty acids
Lipid Digestion: Sites and Enzymes
Sites:1. The stomach2. The small intestine
Enzymes: 1. Act in stomach:
Mouth: Lingual lipaseStomach: Gastric lipase
2. Act in small intestine:Pancreatic enzymes
Lipase and co-lipaseCholesterol esterasePhospholipase A2 Lysophospholipase
1- Digestion of Lipids Begins in the Stomach
The effects of lingual and gastric lipases on TAG:
Little significance in adults (Why?)
Important for digestion of milk fat in neonates and infants (Explain)
2- Digestion of Lipids in Small Intestine
Digestion of lipids is preceded by emulsification
Digestion in small intestine is hormonally controlled:1.Cholecystokinin (CCK)2.Secretin
Emulsification of Dietary Lipids
in duodenumEmulsification increases the
surface area of lipid droplets, therefore the digestive enzymes can effectively act.
Mechanisms:1. Mechanical mixing by peristalsis2. Detergent effect of bile salts:Bile salts interact with lipid particles and aqueous duodenal contents, stabilizing the particles as they become smaller, and preventing them from coalescing
The digestion in small intestine is hormonally controlled.
Two small peptide hormones are released from cells of the upper part of small intestine:1.Cholecystokinin (CCK)2.Secretin
Hormonal Control of Hormonal Control of Digestion in Small Digestion in Small Intestine:Intestine:
Hormonal Control of Hormonal Control of Digestion in Small Digestion in Small Intestine:Intestine:
Cholecystokinin (CCK):
1.Secretion of pancreatic enzymes2.Bile secretion3.Slow release of gastric contents
Secretin:
Release of watery solution rich in bicarbonate by pancreas
CONT’D
The gut hormones:The gut hormones:
The gut hormone Stimulus for
secretion
Effects
1- Cholecystokinin(CCK)
The presence of partially digested proteins (& lipids) in the upper small intestine
1. Stimulates the release of pancreatic digestive enzymes
2. Stimulates the contraction of the gall bladder & release of bile
3. Decreases gastric motility slower release of gastric contents into the small intestine
The gut hormone
Stimulus for
secretion
Effects
2- Secretin Low pH of the chyme entering the intestine
Stimulates the pancreas to release a watery solution rich in bicarbonate to neutralize the pH of the intestinal contents (to reach the optimum pH for digestive activity by pancreatic enzymes)
The gut hormones: The gut hormones: continued…
Pancreatic Lipase and co-lipase
Cholesterol esterase
Phospholipase A2
Lysophospholipase
Pancreatic Enzymes for Digestion of Lipids
Digestion of TAG by Digestion of TAG by Pancreatic LipasePancreatic Lipase
&Colipase
Pancreatic lipase :
Found in high conc. in pancreatic secretion (2-3% of total proteins)
Inhibited by Orlistat, an antiobesity drug
Digestion of Cholesterol Digestion of Cholesterol Ester Ester by Cholesterol Esteraseby Cholesterol Esterase
Digestion of Phospholipids (PL)by Digestion of Phospholipids (PL)by Phospholipase A2 & Phospholipase A2 & LysophospholipaseLysophospholipase
PL Lysophospholipid
Lysophospholipid Glycerolphosphoryl base
H2O Fatty acid
H2O Fatty acid
Phosphophlipase A2
Lysophosphophlipase
Main End Products of Lipid Main End Products of Lipid DigestionDigestion
2-MonoacylglycerolCholesterolFree fatty acids
Absorption of Lipids by Absorption of Lipids by Intestinal Mucosal CellsIntestinal Mucosal Cells
Mixed micelles:Disc-shaped clusters of amphipathic lipids. Arranged with their hydrophobic groups on the inside and their hydrophilic groups on the outside.
Mixed micelle includes end products of lipid digestion, bile salts and fat-soluble vitamins
Short- and medium-chain fatty acids do not require mixed micelle for absorption by intestinal cells
Absorption of Lipids by Absorption of Lipids by Intestinal Mucosal CellsIntestinal Mucosal Cells
Mixed Micelle:2-MonoacylglycerolCholesterolFree fatty acidsBile saltsFat-soluble vitamins
Re-synthesis of Lipids by Re-synthesis of Lipids by Intestinal Mucosal CellsIntestinal Mucosal Cells
1.Activation of long chain fatty acids into acyl CoA
2.Synthesis of TAG from monoacylglycerolCholesterol ester from cholesterolPhospholipids from glycerolphosphoryl base
3.Short- and medium-chain fatty acids are not
converted into their CoA derivatives. Instead, they
are released into portal circulation, carried by
serum albumin
Re-synthesis of Lipids and Re-synthesis of Lipids and Assembly of Chylomicrons by Assembly of Chylomicrons by Intestinal Mucosal CellsIntestinal Mucosal Cells
Assembly of Chylomicrons by Assembly of Chylomicrons by Intestinal Mucosal CellsIntestinal Mucosal Cells
Assembly of chylomicrons:Newly synthesized TAG and cholesterol ester are packaged as lipid droplets surrounded by thin layer of:
Apolipoprotein B-48 (apo B-48)PhospholipidsFree cholesterol
Secretion of Chylomicrons by Secretion of Chylomicrons by Intestinal Mucosal CellsIntestinal Mucosal Cells
Secretion of chylomicrons:By exocytosis into lymphatic vessels around villiof small intestine (lacteals) then enter into systemic circulation
Milky-appearance of serum after lipid-rich meal
Abnormalities in Lipid Digestion/Absorption
Liver and gall bladder diseases
Pancreatic insufficiencye.g., chronic pancreatitis, cystic fibrosis, surgical removal of the pancreas
Intestinal diseases:e.g., Intestinal resection (shortened bowl)
incomplete digestion & absorption of fat & protein abnormal appearance of lipids (steatorrhea) & undigested protein in the feces (Malabsorption syndrome)
Cystic Fibrosis
It affects most critically the lungs, and also the pancreas, liver, and intestine. It is characterized by abnormal transport of chloride and sodium across an epithelium, leading to thick, viscous secretions.
The name cystic fibrosis refers to the characteristic scaring (fibrosis) and cyst formation within the pancreas, first recognized in the 1930s
Cystic Fibrosis …. CONT’D
Autosomal recessive disorder due to mutation to the CF Transmembrane conductance Regulator (CFTR ) gene
CFTR protein is a chloride channel on epithelium
Defect leads to decreased secretion of chloride and increased reabsorption of sodium and water
In the pancreas, decreased hydration results in thickened secretions which cannot reach intestine, causing pancreatic insufficiency
Take home messageTake home message
Dietary lipids are relatively hydrophobicLipid digestion begins in stomachEmulsification of lipids occurs in duodenum,
helped by peristalsis and bile saltsIntestinal digestion of lipids by pancreatic
enzymesLipid absorption by formation of mixed
micelles
Take home messageTake home message
Re-synthesis of TAGs, cholesterol ester and PLs inside the intestinal mucosal cells
Assembly and secretion of chylomicrons into lymphatic lacteals and then into systemic circulation
Short- and medium-chain fatty acids:Do not require micelle for absorptionDo not participate in re-synthesis of TAGs & PLsReleased directly from intestinal cells into portal circulation
CONT’D
Take home messageTake home message
Liver diseases, pancreatic insufficiency, or intestinal diseases incomplete digestion and absorption of fat & protein steatorrhea & appearance of undigested proteins in the feces (Malabsorpton syndrome)
CONT’D